Neurology® Podcast

Dr. Tesha Monteith talks with Dr. Tamara Pringsheim about the updated American Academy of Neurology (AAN) and American Headache Society (AHS) guidelines on pharmacologic treatment for migraine prevention in adults. 
Read the related article in Neurology®.
Disclosures can be found at Neurology.org. 
Show transcript: 
Dr. Jose Merino (00:08):
This is Jose Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week.
Dr. Tesha Monteith (00:23):
Hi, this is Tesha Monteith with the Neurology Podcast. I'm excited to talk to you today about the update in Migraine Guideline: Pharmacologic Treatment for Migraine Prevention in Adults: Practice Guideline Recommendations, a report of the American Academy Neurology Guidelines Subcommittee, and the American Headache Society. Since the last guideline in 2012, there's been a lot of new advances, including the introduction of CGRP inhibitors for acute and preventive treatment.
(00:53):
With me to discuss is the lead author, Tamara Pringsheim, a neurologist at the Department of Clinical Neurosciences, Psychiatry, Pediatrics, and Community Health Sciences at the University of Calgary. How are you, Tamara?
Dr. Tamara Pringsheim (01:06):
Great. Thank you for asking me to talk to you about this.
Dr. Tesha Monteith (01:09):
Why don't you tell me a little bit about yourself and how you got involved in this work?
Dr. Tamara Pringsheim (01:14):
Sure. I've been working as a methodologist for the American Academy of Neurology Guidelines Subcommittee for a number of years, since 2015. Prior to that, I was a member of the guideline development subcommittee from 2011. I've worked on a number of different guidelines across neurological conditions.
Dr. Tesha Monteith (01:36):
Great. So how do these new guidelines compare, just broadly speaking, with the older guidelines?
Dr. Tamara Pringsheim (01:43):
I guess since the last guidelines were published more than 10 years ago, we've had changes to our methodological process. We had a major update to our guideline process manual in 2017, and guideline methodology has continued to evolve over that time period. And as well, a number of targeted treatments for migraine have come out. So there's been an explosion of evidence, particularly in the last five to seven years. And so we have a whole new class of medications available for migraine prevention, which really target our underlying understanding of the condition, whereas most of the other medications were discovered through serendipity.
Dr. Tesha Monteith (02:33):
So I know that you reviewed over 200 randomized controlled trials. And so how was the quality or confidence of the evidence determined?
Dr. Tamara Pringsheim (02:47):
With our process, we start by rating risk of bias for every article. This basically gets at a number of different features related to the clinical trial methodology and reporting, and it helps us determine how confident we are in the evidence. In order for us to be highly confident that the results that we are seeing reflect the truth, we typically need to have at least two Class 1 studies for any intervention outcome pair. The effect size estimate also has to meet a certain threshold in terms of the effect size and the precision surrounding that estimate. So if we feel that based on what the panel decides in terms of what is the minimal clinically important difference between an intervention and placebo, that will help us determine our confidence in the evidence.
(03:51):
So there's this critical coming together of the number of studies, the quality of studies, the effect size, and the precision of the evidence that helps us determine our confidence in the evidence. And all of this is done behind the scenes using a very algorithmic approach so that these rules are faithfully applied across the different interventions we're looking at. This complexity makes it hard for people to understand why certain drugs land in a certain area, but it's one of the things that we do to make this process standardized and rigorous.
Dr. Tesha Monteith (04:37):
So I do want to talk to you about that, where drugs have landed. One newer thing was that the review was not just episodic migraine, but also chronic migraine.
Dr. Tamara Pringsheim (04:47):
Yes.
Dr. Tesha Monteith (04:48):
Were there important differences in the strength of evidence between these populations?
Dr. Tamara Pringsheim (04:53):
One thing that's really important to remember is that the use of the term chronic migraine is fairly new. So a lot of the trials of the older headache preventive medications were done in the 80s and the 90s. And at this time, there wasn't a definition which distinguished chronic migraine in particular. So a lot of the trials for amitriptyline, for example, were not done in a purely episodic or chronic migraine population. And so this really contrasts with the newer studies where these populations were well-defined. And so we're going to have higher quality evidence or evidence specifically for chronic migraine with the new drugs, whereas for the old drugs, we won't have that.
Dr. Tesha Monteith (05:50):
Let's get into the preventive treatments that had the strongest level of evidence for episodic migraine.
Dr. Tamara Pringsheim (05:57):
We had high confidence in the evidence for two of the CGRP medications, erenumab and galcanezumab. Again, these high confidence in the evidence statements are based on the fact that for both these drugs, there were multiple Class 1 studies showing that they were efficacious. And the effect size was in the range that was pre-specified. So the lower level of the 95% confidence interval was clearly higher than what we decided was the minimal clinically important difference. Both these drugs, one had two Class 1 studies, one had three Class 1 studies, so we could be very highly confident that these two medications were efficacious.
(06:50):
Now for the moderate confidence drugs, we have a longer list for episodic migraines. So it includes atogepant, eptinezumab, fremanezumab, propranolol, rimegepant, topiramate, and valproate, and then a slightly longer list for the low confidence drugs. So amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan.
(07:18):
And for this outcome, I'm specifically talking about episodic migraine headache days. Now, one of the layers of complexity, again for this guideline, is that we had a few different outcomes that we were looking at. So the two main outcomes we were looking at were the headache frequency, the change in the number of headache days, but also the 50% responder rate. That's the proportion of people in the treatment group who had at least a 50% reduction in their headache frequency. And some drugs would make it for one endpoint, but not the other. And this is an important nuance that, again, adds complexity to our data synthesis.
Dr. Tesha Monteith (08:06):
And what about for chronic migraine?
Dr. Tamara Pringsheim (08:08):
So for chronic migraine, for the number of headache days, we had high confidence for fremanezumab, galcanezumab and onabotulinumtoxinA, and moderate confidence for atogepant, eptinezumab, erenumab, topiramate, rimegepant, and valproate. We didn't have any medications that were in the low confidence in the evidence category.
Dr. Tesha Monteith (08:33):
Oftentimes in the newer clinical trials, we're looking at change in monthly migraine days, but interesting that you looked at headache days.
Dr. Tamara Pringsheim (08:42):
Yeah. So another difficulty is that there's not always consistency in what's reported. So some trials would report headache days and some trials would report migraine days per month. Wherever possible, we use the change in the number of days with migraine. And where this was not present, we would use headache days.
Dr. Tesha Monteith (09:08):
Now, a drug that we use very often in clinical practice is rimegepant, which has a dual benefit of acute attack treatment as well as prevention. And that was rated as low confidence, but in a recent International Headache Society, Italian guidelines, that was noted as moderate quality evidence, strongly in favor of. What do you think that discrepancy was about? Is that a matter of outcomes or?
Dr. Tamara Pringsheim (09:38):
This guideline includes clinical trials that were published up until June of 2024. And so at that time, the only trial of rimegepant versus placebo that was published was in a population of patients that had episodic or chronic migraine. The population was combined. And so we only have one study. And as I was explaining at the beginning, in order for us to have high confidence in the evidence, we have to have at least two Class 1 studies and the minimal clinically important difference has to meet a certain threshold. So for rimegepant in June of 2024, there's only one study published versus placebo. So the highest possible confidence in the evidence we could have for rimegepant based on the fact that just one study would be moderate.
(10:38):
The reason why it's not listed in recommendation 3A as high or moderate confidence is because while we had moderate confidence in the evidence for rimegepant on the number of headache days, we had low confidence in the evidence for the 50% responder rate. And that's because for the 50% responder rate, it did not meet the pre-specified cutoff with respect to the minimally clinically important difference.
(11:11):
So again, it's a small nuance in the evidence, but for an evidence-based guideline, we really pay attention to these things. I know it makes it complex and hard for people who are not immersed in the evidence to understand. This is part of the rigor. There's a temptation to oversimplify things so that it's easy to understand, but that's really one of the strengths of the AAN process is that we take the evidence very seriously. We are truly evidence-based. We are going through every data point very carefully, and so that you should feel confident when you see that we've rated these medications as a higher moderate confidence, that we've really looked and evaluated these data points very carefully.
Dr. Tesha Monteith (12:01):
We can say that different guidelines have different outcomes. And to your point, it's more than just the data. It's your pre-specified process that then led to those recommendations, right?
Dr. Tamara Pringsheim (12:14):
Yeah. And I feel pretty confident that if we were to update the evidence, including the last two years, that rimegepant would move up, right? Because just looking even quickly now, we can see that since 2024, there have been several additional studies published. So now we wouldn't just be basing our evidence review on one placebo controlled study. There have been several more, the medications FDA approved.
Dr. Tesha Monteith (12:44):
Right.
Dr. Tamara Pringsheim (12:45):
I don't think anyone should change their practice based on this and people should be using rimegepant. That's not the message that we're trying to send.
Dr. Tesha Monteith (12:54):
That's really important.
Dr. Tamara Pringsheim (12:55):
Yes. We are not on a campaign to say that rimegepant is not a treatment option. As you can see, it is listed and it is in the guidelines. It's just based on the data we had available, we had low confidence in one of the outcomes, the 50% responder rate. So I hope that makes sense.
Dr. Tesha Monteith (13:14):
Yeah, I think it makes sense. It's the processes, it's a 2017 guideline manual, and that does make sense. So thank you for that clarification because a lot of our clinicians will be asking questions about this.
Dr. Tamara Pringsheim (13:26):
I mean, the same goes for another drug, candesartan is the other one.
Dr. Tesha Monteith (13:30):
Yeah. Candesartan recently had a paper published in the Lancet.
Dr. Tamara Pringsheim (13:33):
Yes.
Dr. Tesha Monteith (13:33):
And it did well, and people are using candesartan.
Dr. Tamara Pringsheim (13:38):
Yes. Yes, exactly. I prescribe candesartan for migraine prevention. At the time we did the evidence review, we had a couple of positive studies, a couple of negative studies. And when we put the data together, it came out as very low confidence because there's a discrepancy. And then we have a huge trial published that is a positive study, but it came out in 2026. It was not part of our evidence review. We don't say anywhere in the guideline, don't use candesartan, right? We don't say that. We highlight the drugs for which we have the confidence in the evidence and put them in there. But we need to remember that new drugs are coming out all the time and that they didn't factor into our decision making.
(14:26):
So again, I hope that people don't read the guideline and say, "Oh my God, I can't use candesartan." That's not true.
Dr. Tesha Monteith (14:33):
So one thing I want to look at is quality of life outcomes. That was something also not seen in the first or the 2012 guidelines. And so how did you look at quality of life outcomes and how should we consider them?
Dr. Tamara Pringsheim (14:47):
Yeah, so we wanted to make sure that we incorporated patient reported quality of life outcomes in the guideline, recognizing that this is very important. And the newer trials of the more recent medications have been incorporating patient reported quality of life outcomes in their clinical trials. This adds overall credibility that we are incorporating into our decision-making evidence that not only are patients' number of headache days decreasing, but their quality of life is improving because that's important to patients and hence is important to us.
(15:31):
So we used outcomes from validated measures of migraine related quality of life. So there's the MIDAS, there's the HIT-6, and there's something called the migraine specific questionnaire, which has three subscales. One is emotional function, one is role function preventive, and one is role function restriction. And then a few studies use something called the migraine physical function impact diary. So those were the main instruments that we looked at. And again, we had a pre-specified minimally clinically important difference on these instruments that we looked at.
(16:19):
And we had a reasonable amount of data, not as much data as we had for headache days or the responder rate, but certainly again, for the CGRP antagonists, we had high confidence in the evidence for galcanezumab, for example, in episodic migraine. And for chronic migraine, we had moderate confidence in the evidence for a number of medications including topiramate and onabotulinumtoxinA. So these quality of life measurements seem to be increasingly used in our modern clinical trial era.
Dr. Tesha Monteith (17:07):
Great. Another question is just thinking about some of the limitations of this work. There were very few high quality head-to-head trials. How does that limit your comparative effectiveness data?
Dr. Tamara Pringsheim (17:19):
This is a major issue that most, but not all of the head-to-head trials were investigator-led. Many were done a very long time ago before the modern clinical trial era, and so the quality of these studies was low. And also they were not non-inferiority studies. So basically the only question they could answer is whether drug A is better than drug B based on their trial protocol and methodology. And for most of the comparisons, we have very low quality evidence, so we really cannot support or refute that drug A is better or worse than drug B. So we can't really say anything. There were a few instances where we could say that drug A is better than drug B, but it's low confidence evidence, very few comparisons.
(18:17):
Some evidence is emerging so that some of the CGRP drugs are being compared to some of the older drugs now with the hope that we can prescribe these sooner to migraine patients. That evidence will probably emerge in the coming years.
Dr. Tesha Monteith (18:31):
And another question is how should these guidelines be incorporated in clinical practice also while balancing tolerability, comorbidities, patient preference, reproductive considerations, access, and costs?
Dr. Tamara Pringsheim (18:47):
So we have the evidence synthesis. So you can say, okay, this is the evidence. These are the effect sizes. This is the number of studies to support this outcome, that outcomes. You have the details in the systematic review, right? And then how do you take those details and apply them in the practice? And that's the art of medicine. And we don't make decisions without our patients. All of our decisions are collaborative. I say to my patients, "It's my job to tell you what your options are. It's your job to discuss these options with me and for us to make a decision together regarding which one is the best for you in your situation."
(19:30):
And that's what we're trying to do in the recommendations. In the recommendation statements, you'll see that in this specific situation, this might be a better choice. We talk a lot about when you're going to decide to even start a preventive and the importance of shared decision making, that those are our first two sets of recommendations. Recommendations one and two are about those things.
(19:56):
And then our recommendation three statements just tries to gently offer some advice on when you should think about which medication, where efficacy is the priority, tolerability is the priority, long-term harms, cost. Cost is a really tricky one because cost really depends on the person's specific pharmaceutical formulary plan and healthcare insurance. I know that for some patients, their insurance plans require a certain number of oral medications to be tried before an injectable like a botulinum toxin or a subcutaneous medication or one of the newer medications can be prescribed.
Dr. Tesha Monteith (20:41):
So you put a lot of work in this, your team, the American Academy of Neurology, the American Headache Society, outstanding work. What should we take away from this?
Dr. Tamara Pringsheim (20:52):
I think that we should take away that a lot of work is being done by headache neurologists and neuroscientists who are interested in headache to develop new treatments for people with migraine. I think that the CGRP drugs are a major advance and that now we have many new medications that are specifically designed for migraine treatment and these treatments are changing people's lives for the better. I think it's brought new hope to people with migraine and it's an exciting time to be a clinician who treats patients with migraine when you have several new medications where the companies have invested the time to do the research, do well-designed clinical studies, and that we can feel confident that these medications are helping our patients.
Dr. Tesha Monteith (21:51):
Excellent. I couldn't have said that better. Thank you again for your work and your time and for being on our podcast.
Dr. Stacey Clardy (22:00):
This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword on the podcast app for any neurology specific topics.

Dr. Justin Abbatemarco talks with Dr. Irene Cortese about recent advances in the treatment of progressive multifocal leukoencephalopathy (PML), focusing on immune-based therapies like virus-specific T cells and immune checkpoint inhibitors. 
Read the related article in The New England Journal of Medicine. 
Disclosures can be found at Neurology.org. 
Show transcript: 
Dr. José Merino:
This is José Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening, and have a great week.
Dr. Justin Abbatemarco:
Hello and welcome. This is Justin Abbatemarco with the Cleveland Clinic here with Irene Cortese to discuss an update on progressive multifocal leukoencephalopathy treatment in light of a New England Journal of Medicine correspondence, Resolution of PML After Treatment with Virus-Specific T Cells and HCT. Irene directs the Experimental Immunotherapeutics Unit at NINDS. Hello and welcome.
Dr. Irene Cortese:
Hi, thank you for the invitation to join you today.
Dr. Justin Abbatemarco:
It's a pleasure to have you on and to talk about this expanding space in rare disease. And maybe if we could start off, can we just take an overview on how PML usually presents and why does it remain so difficult to treat?
Dr. Irene Cortese:
PML, or progressive multifocal leukoencephalopathy, is an opportunistic infection of the brain that is caused by the JC virus. And most of us carry this virus lifelong and without any symptoms, and it really only causes disease when the immune system is significantly compromised and loses the ability to keep it in check. And so when that happens, the virus can gain the ability to infect oligodendrocytes, and this can lead to the rapidly progressive demyelinating infection called PML.
These lesions that develop in PML are typically located in the white matter, and they are most often multifocal. And this leads to the clinical manifestation of a combination of cortical and subcortical symptoms that evolve over weeks to months. And, unfortunately, if immune competence can't be restored quickly, then the disease is fatal within just a few months. And so that's really the core of the problem here, is that there is no effective direct antiviral treatment. And the only thing that works is restoring the immune system ability to control it, but that's often very difficult to do. When it's even possible, it's frequently just not even fast enough.
And so you can see this even in situations where you'd think that we'd have an advantage, for example, in HIV-associated PML, where we do have effective antiretroviral therapy. Even there, restoring immune competence can sometimes just take too long relative to how quickly PML progresses.
And so on top of all that, PML is really quite rare and is also remarkably heterogeneous because it can occur in very different patient populations from HIV to hematological malignancy to genetic immune deficiencies. And this rarity and heterogeneity really make both the diagnosis difficult and also treatment development quite difficult.
Dr. Justin Abbatemarco:
It's such a interesting story, and these different backgrounds really present different challenges. But at these last few years, this has been a success story in some way because we've seen so much effort and research into this rare disease space, which is encouraging. We mentioned this at the top, but there are immune checkpoint inhibitors that have at least been trialed for this T cell exhaustion to see if we can boost the immune system, and then more recently with your work around allogeneic-specific T cells to help clear the infection. What have you taken away from those updates?
Dr. Irene Cortese:
The biggest takeaway is that these two approaches, checkpoint inhibitors and Virus-Specific T Cells, have really transformed the way that we think about PML. So for decades, our only option was really to try to reverse the underlying immune suppressive condition and just hope that the immune system caught up in time. And now we have these two active strategies to try to speed this process up.
Importantly, both these strategies have validated the same core hypothesis that even without a direct antiviral agent, we can improve PML outcomes by restoring effective antiviral immunity. And that said, each of these approaches has real limitations. So first of all, they don't work in all patients. And we have best estimates of success rates somewhere in the 50 to 60% range overall. With checkpoint inhibitors, the fundamental issue is that you're trying to unleash an immune response that has to already be there in some latent or exhausted form.
For example, in patients with very advanced immune compromise where the T-cell compartment is essentially absent, there's just nothing left to invigorate, and so checkpoint blockade is really unlikely to help. And even when they do work, there is a real risk of exacerbating underlying autoimmune disease as well as the risk of leading to immune reconstitution inflammatory syndrome, or IRIS, where inflammation in the central nervous system of this immune system waking up and attacking the infection can actually lead to severe morbidity and even death in some patients.
Virus-Specific T Cells have a whole different set of limitations. These are mostly practical and logistical at this point. Access is really the big one because there are only a handful of centers worldwide that can manufacture Virus-Specific T Cells. And so this just isn't something you can easily do everywhere or quickly. And also, biologically, every virus-specific T-cell product which is made from a different donor is essentially a different drug. And so it's really hard to predict how any given cell product will actually behave in a given patient.
I should also mention that for both these approaches, they truly are still experimental. We don't have any controlled studies, and so most of what we're working from is really retrospective series and case reports. And we definitely have no head-to-head data. And so while we apply general principles estimating residual immune capacity or weighing the risk of exacerbating immune-mediated adverse events, we're really making individualized judgment calls rather than following an evidence-based algorithm.
Dr. Justin Abbatemarco:
And could you talk about those Virus-Specific T Cells? It's not something we use commonly in neurology. How do those work? And have they been used in other spaces successfully that we've been able to maybe apply some of those principles here?
Dr. Irene Cortese:
Yeah. So Virus-Specific T Cells were really first developed in the transplant setting, and they were essentially a way to bridge patients immediately following myeloablation. And in the period of time it took them to fully immune reconstitute a brand new immune system, it was a way to protect them from the common viral infections mostly that can develop in this time period and that led to such high morbidity and even mortality.
And so the way this is done is that you basically take healthy lymphocytes from a healthy donor, and you can train them in vitro by ex vivo expansion and stimulation to basically become professional killers of the particular virus of interest so that, at the end of this expansion period, you basically have a enriched antiviral product that can be adoptively transferred to the patient recipient. And they may not last for a very long time, however, they can, especially with repeated infusions, provide the necessary immunity to bridge until definitive immune reconstitution is achieved.
And so the initial experience with Virus-Specific T Cells was really against the various viruses that are so common in the post-transplant setting, like CMV, EBV, adenovirus, and also BK virus, which is a cousin, let's say, of the JC virus. And over time, the process for manufacturing Virus-Specific T Cells has become more and more streamlined. And so back as in 2015, 2017, we started to realize that perhaps these types of cell products might even be used to treat an acute infection and not just to administer in the setting of a planned transplant.
And so essentially we've done exactly this, basically copied these manufacturing methods from the transplant world to make Virus-Specific T Cells against the JC virus and can then use them to treat PML. I should mention that BK virus is very similar in structure to the JC virus. And for that reason, what we learned early on when we started to apply Virus-Specific T Cells to the treatment of PML was that we could actually use Virus-Specific T Cells that were made against BK virus and successfully treat PML. More recent years, groups have been manufacturing JC virus-specific BST, but those BK Virus-Specific T Cells can still be used to treat PML.
Dr. Justin Abbatemarco:
That's really incredible. And it's so cool when we borrow things from these other fields to help inform rare diseases within neurology space. Maybe it's a perfect segue into the cases report in New England Journal of Medicine where you had two cases with inborn errors of immunity. You've utilized the strategy and then stem cell transplant. Walk us through those cases. What did you see? What did we learn from these that we can apply more broadly?
Dr. Irene Cortese:
Our paper really told the story of our experience of treating these two young men. Both of them had developed PML in the setting of an inborn error of immunity. One of them had DOCK8 deficiency, and he also had Sézary syndrome as a comorbid condition. And the second patient had a CD40 ligand deficiency.
And for both these patients, we basically adopted the same strategy, which was to first try to gain control of the JC viral infection. And once that infection was actually under control, then we went ahead and proceeded to definitive treatment of their underlying genetic immune deficiency, which was transplant in their setting to correct the real root problem that they had.
And what I think was perhaps most instructive in this experience is what happened after transplant in both cases. So transplant obviously involves a period of renewed immune vulnerability, and that's exactly when we feared that the PML might come back, even though we had been able to gain control, at least temporarily, using this adoptive transfer Virus-Specific T Cells.
Fortunately, in these two cases, that didn't happen. And in fact, patient one actually developed IRIS shortly after engrafting with worsening neurological symptoms and also imaging that showed active inflammation, which responded well to steroids. And he's now years out with no evidence of PML or his prior malignancy, which was also treated by the transplant.
The second patient's course was complicated by cryptogenic organizing pneumonia, or COP, which can happen in the post-transplant setting, and did require steroids. And this did cause a transient uptick in the JC viral copy number in the spinal fluid, but this resolved once the steroids were tapered. And this patient also is now several years out with only mild residual neurological deficits. So it's important that for both these patients, the transplant donors, in addition to undergoing collection for the transplant itself, they also underwent a collection to make extra rescue Virus-Specific T-Cell products that we had on hand just in case the PML relapsed post-transplant, which of course was not, in the end, needed.
And so basically, the overall strategy for both these patients was sequential and deliberate. First to establish virus-specific immune control, and only then proceeding to the definitive but higher risk step of transplant with the safety net available in case virus reactivated during that post-transplant period.
Dr. Justin Abbatemarco:
The complexity of these cases, though, and the successful outcome is just incredible. And again, we don't always treat these level of patients, but most neurologists will see PML during their career. How do you think this helps inform this broader field of PML treatment in your mind?
Dr. Irene Cortese:
For me, these two cases really crystallized the idea of immune facilitation as a bridge rather than as a standalone endpoint. For example, in these two patients, Virus-Specific T Cells could not have led to a definitive cure because the underlying immune defect was still there, but they could buy time and control the virus long enough to get to something that could actually fix the underlying problem, which in this case was the transplant.
And I'll be honest, proceeding to transplant in a patient with active or recent PML was really frightening. And clearly that is not an option or appropriate at all for the majority of patients with PML. So I guess that the broader lesson here is that Virus-Specific T Cells or potentially other immune-facilitating strategies might serve as a bridge to get us to the point where we either have a way to address that root cause of immune suppression or just buy us the time needed to recover from immune suppressive exposures and perhaps opens up the question of how we might use sequential strategies and combinations of strategies to optimize the care of these patients.
Dr. Justin Abbatemarco:
Really appreciate your paradigm of how you think about these cases in treatment, and yet you can have these short-term strategies to bridge patients to have an improved immune response to get this under control. Could we talk about other common examples? So we have natalizumab-induced PML cases, HIV-associated PML cases. How would you think about managing those, so outside of these inborn errors of immunity?
Dr. Irene Cortese:
Each PML patient is somewhat unique, and definitely the underlying condition that is driving the immune suppressed state is really critical in mapping out what we need to do. I think of HIV-associated PML or even natalizumab-related PML as being somewhat unique. Because unlike most other causes of PML, we actually do have clear and reliable ways to restore immune competence, so basically antiretroviral therapy in HIV infection or simply discontinuing the non-immune-depleting drug natalizumab in the case of natalizumab-related PML. And so this is obviously a real advantage compared to many of the other underlying conditions where there really is no good way to reverse that immune suppression at all.
That said, in some patients, for example, with advanced AIDS and very low CD4 counts, immune reconstitution can still be very slow even when the HIV replication itself is well controlled. And so in a subset of patients, the PML can still really pace the recovery. And so we do sometimes need strategies to bridge that gap. And basically. we would consider the same immune restoration approaches that we've been talking about right now.
There is an added layer of complexity here that's a bit more, let's say, unique to HIV-related PML or to the setting of natalizumab-related PML, which is that in both these cases, immune reconstitution is going to happen eventually. And when it does, then many of those patients do experience PML IRIS where the constituting immune response paradoxically worsens the neurological injury by attacking the infected tissue. And so this really needs to be watched for and managed typically with steroids. And certainly this risk of developing PML IRIS needs to be really considered if we are going to use strategies to boost or facilitate immune reconstitution in the setting of HIV infection or natalizumab-related PML. And we just have to be particularly mindful because there's already a very high likelihood of developing PML IRIS independently of getting that extra boost.
Comparatively, in the setting of non-HIV-related PML or not in the setting of natilizumab treatment, I think that strategies like checkpoint inhibition and Virus-Specific T Cells have really been game-changing because, historically, these patients had no equivalent to antiretroviral therapy with no reliable path to reconstituting immunity. And we're really hoping that these approaches will start to bring the outcomes that we've seen, for example, among HIV-related PML and in the setting of natalizumab and PML to these other underlying conditions and achieve the same immune control and survival rates that are achieved in at least a substantial portion of these patients.
Dr. Justin Abbatemarco:
It's been so exciting. Again, the updates in this field when we really did... We had nothing to offer patients for so long and now to have conversations that are a little bit different. Can I ask you to peer around the corner? What does the future look like in your mind? Do you see other therapies that are potentially at play and maybe right now are there clinical trials that we could enroll patients so that we can help inform the field more broadly?
Dr. Irene Cortese:
Yeah. So I think that ways to facilitate and accelerate immune reconstitution have clearly been shown to be a valid strategy. And so what I expect and hope is that in the years to come, we'll learn to harness that better and learn to identify which patients are most likely to respond to particular types of strategies to facilitate immune reconstitution.
It's really important, I would say, that patients participate in trials because the field really does lack controlled data and it lacks head-to-head comparisons. And so every patient enrolled in a trial or a well-structured registry is really contributing to how the next patient gets treated. And given just how rare and heterogeneous PML is, we're just not going to advance this field through isolated case reports alone. And so we really do need patients and their physicians to be willing to participate in structured and collaborative research.
The Holy Grail is, of course, a direct antiviral agent that would really broaden our ability to treat patients and potentially also continue to treat whatever that underlying condition was that led them to the risk of PML in the first place, so, for example, patients receiving treatment for cancer or patients having an autoimmune disease that requires immune suppression. And so I am hopeful that eventually the direct antiviral will be identified.
And along that line, what I can mention is there are certainly clinical trials that are ongoing. At NIH, we have an active natural history study from where we can funnel patients into various experimental treatment strategies, including Virus-Specific T Cells or checkpoint inhibitors. Or right now, we actually do have an ongoing trial of intravenous brincidofovir as a possible direct antiviral strategy. What I hope for the future is that we will find ways to really collaborate and to form national as well as international consortia so that we can accelerate the development of these treatments.
Dr. Justin Abbatemarco:
We have things we can do now, and then we can help inform care for our future patients as well. So these are great messages, and I can't thank you enough for coming on. Again, most of these developments have been under your guidance, and we appreciate your leadership in this space and helping to give us this insight into this really rare disease. For folks, they can check out the article. It's in the New England Journal of Medicine, Resolution of TML After Treatment with Virus-Specific T Cells and HCT. Irene, thank you for coming on.
Dr. Irene Cortese:
Thank you so much.
Dr. Stacey Clardy:
This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org\podcast for our full list of past episodes, or you can also search by keyword on your podcast app for any neurology-specific topics.

Dr. Kait Nevel talks with Drs. Ayal Aizer and Clara Baselga-Garriga about the link between primary motor cortex involvement in brain metastases and increased seizure risk, highlighting implications for patient management and future research directions. 
Read the related article in Neurology®.
Disclosures can be found at Neurology.org.

Dr. John Ney talks with Dr. Daniele Piomelli about the evolving role of cannabis in neurology, exploring its history, current research, and potential future applications.
Read the related article in The New England Journal of Medicine. 
Disclosures can be found at Neurology.org.

In part two of this two-part series, recorded at this year's AAN Annual Meeting, Dr. Gregg Day talks with Drs. Joel Salinas and Sarah Song about imperfect but practical brain health metrics, patient-centered assessment strategies, and future directions in brain health assessment. 
Visit the newly launched BrainHealth.com to access trusted brain health information and stay informed. 
Disclosures can be found at Neurology.org. 
 
Show transcript: 
Dr. Jose Merino:
This is Jose Merino, Editor-in-Chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening, and have a great week.
Dr. Stacey Clardy:
Hi, this is your Podcast Editor, Stacey Clardy. Today we feature part two of the brain health discussion that took place at the AAN annual meeting a few months ago. If you have not yet, take a listen to part one from this past Thursday's podcast. For this episode, we pick up with the discussion focusing on plans for how to implement and measure effectiveness of brain health interventions, the sort we can all undertake easily in our clinic visits.
And then, we wrap up the episode with comments and questions from the audience who were present at the Brain Health Talk. I hope you take away some inspiration and some ideas on how to encourage your patients to be proactive about protecting their brain. Thanks. Enjoy.
Dr. Gregg Day:
Hello, this is Gregg Day from Mayo Clinic, and welcome to this special conversation. Today's episode is recorded live at the Brain Health Hub during this year's AAN Annual Meeting in Chicago. Because it was recorded on site, the audio may sound a little different from our usual episodes, but bear with us because it's absolutely worth it. This panel discussion is totally aligned with AAN's mission of bringing brain health to all, and on point with the release of brainhealth.com, AAN's new website, bringing together our resources for clinical practice and for research in this space. We hope you enjoy this panel discussion as much as we enjoyed recording it.
One thing that we acknowledge on the Brain Health Committee, one thing that the AAN is committed to fix as we move forward, there's a lack of validated brain health metrics and biomarkers when we talk about brain health. So what does it mean to be healthy? Or maybe a better question, what does it mean to be healthier than I was a year ago headed in the right direction or trending in the right direction? Joel, your thoughts, what should neurologists measure today, even if it's imperfect, that can help us move brain health from concept to more of an accountable practice?
Dr. Joel Salinas:
This point about imperfect is actually really critical. I think when we're thinking about measurements, there's a trap that we tend to fall into, which is trying to identify the perfect measurement. And I often see that as an excuse to not measure at all. And so, thinking about what is it that you can most practically take into account today. And there's so many different measures for so many different elements, and I would just encourage you to think about what's most relevant to the patient in that moment, and that would be the ideal tool.
There's things like the PHQ-9. There's all these cognitive screening assessments. There's different measures related to cardiovascular risks that are out there. Even though none of those are perfect, right? None of those are perfect, we've been able to move healthcare forward quite a lot using these imperfect measures. So I would encourage you to find what is your toolkit of measures that are most helpful for you.
Actually, one of my favorite measures, going back to sleep, is actually not metric itself. It's actually just asking, how are you sleeping? And getting that qualitative data because we forget that metrics don't have to be quantitative, they can be qualitative as well. We often will collect things like the GAD-7, the PHQ-9. There's a UCLA 3-item Loneliness Scale. But when I'm in clinic, I'll often just ask, "Have you been feeling lonely?" Or, "How often are you feeling lonely?" And that in and of itself gives you a lot of really valuable information.
Dr. Gregg Day:
Simply asking that question about physical, mental, social well-being and where do you think you are compared to last year? We've spent a lot of money, a lot of investment to try to develop a tool that performs better than asking someone directly, "Do you feel depressed?" It's hard to do that. So yeah, let's not forget our patients in the room as maybe the greatest arbitrators of that progress. Sarah, any other things that you're thinking of along these lines?
Dr. Sarah Song:
I still go back to what Joel was saying earlier about individualizing it to the patient and getting more details on something that they happen to mention about if they're feeling lonely or if they mention their sleep, and then delving further into that. As a stroke neurologist, what's really easy for me is I always ask how they're sleeping, I ask how their mood is, and I just go into the markers of depression that we all learn about that are not necessarily just mood. But I ask, obviously, how they're sleeping, how they're eating, do they have energy, what exercise are they doing, what therapy are they doing?
And those for me are natural as part of the conversation of post-stroke, but that they touch upon a lot of the elements of brain health already. That's what's really key. Brain health isn't something new, it's actually something that we're already measuring and we're already looking for and we're already asking. Being able to put any sort of, I know it's not qualitative, but putting any sort of number to it or any sort of marker that we can use to measure it and even asking, "Last year you mentioned that you weren't sleeping very well. Do you think that you're sleeping better now or is it worse?" or, "What changed?" Right?
Dr. Gregg Day:
I think we're talking about setting goals with our patients that we can then ask, "Are we attaining those goals? Are we maintaining those goals?" We can begin that process together. That's really important, very practical. Thank you, guys.
We talk about brain health, we talk about quality, and quality of evidence here, and we can appreciate that really matters and is challenged by the multitude of sources of evidence and various levels of quality that we have.
Joel, you hit the nail on the head with this encouragement to not let perfect become the enemy of good. And so recognizing that, how do we navigate some of these challenges when we're talking about interventions that patients are bringing forward or maybe that we're interested in trying out?
We think there might be some role for those, albeit imperfect. So how do we navigate the uncertainty while maintaining credibility and building trust with our patients about making these recommendations towards brain health?
Dr. Joel Salinas:
Neurology, in particular, we all develop an expertise in navigating uncertainty. When it comes to brain health, it's just bringing some of those tools and perspectives into that space as well, right? Because we're always talking about prognosis and what to expect and building trust with patients. They're not really looking for you to be certain. Right? They're looking for you to be honest about that uncertainty. The more you're able to actually very clearly articulate to them, "This is what we know about this, this is what we don't know, and this is directionally what we think is helpful." And that applies within the brain health space as well. Right?
We don't have huge randomized clinical trials around all the different intervention. The U.S. POINTER study from last year was really helpful in pointing in that direction. From all the literature that we have, we do have a sense of direction. Maybe we don't know the magnitude of effect quite yet, but we can at least point people in the right direction towards things that can be most helpful for them. And then, couch it within how certain we are based off of the evidence. And I will say, most of the time that I bring up issues of uncertainty, patients will respect and trust more me as a clinician than I'm being honest about what I know and what I don't know, and how we're navigating things together.
Dr. Gregg Day:
Excellent advice. Do you want to add anything to that?
Dr. Sarah Song:
Neurology is a field that inherently has a lot of uncertainty. We have to be honest and truthful, and we have to listen to our patients. And ideally, we want to be able to promise just good things. Right? I always do caveat with strokes. I'm like, "We're going to do everything we can to help prevent another stroke. Nothing brings the risk down to zero, but we're going to do everything we can to move that needle in your favor." And being honest and truthful does go a long way, but you should never assume that you're God, and that you can fix everything. Nobody can.
Dr. Gregg Day:
There's that element of humility that we're all expressing here, which is very important. This is a great opportunity to hear from you guys. It can be a question for the panel, that's totally fine. It can be a story that you want to share, your own experience to brain health. Maybe it's the challenges that you're dealing with in clinic. Or maybe it's a success and just an incremental move in the right direction, something that you've already seen.
So if you would like to share something, you just put up your hand, and be prepared to catch because this square is coming your way. That's the goal. So we're really hoping we get to see somebody actually catch this. Oh, here we go. Our first candidate, Dr. Lazar. Yes.
Dr. Lazar:
Hi, everyone. So PGY-3, neurology resident. And I recently did my rotation in Generative Psychiatry, and it was a very important case. We have a demented patient who were just, like, demented but suffers for a major depression. And inpatient psychiatric unit with treatment, we handled the depression and his MoCA score improved. So it's very important to really realize that how much the psych component can affect these people.
And all three of you mentioned the mental issue when it comes to dementia patients. But in our practice it's less established to work with psychiatrists altogether or having a comprehensive group of people. For example, the patient who has an ALS, they have a comprehensive group of people like speech therapy, movement, and PT. We need that too when it comes to dementia. And we need to work closer with psychiatric issues and correct cognitive elements.
Dr. Gregg Day:
You're pointing to, generally, the later life stage, the senescence life stage, which has its own complications in neurodegenerative disease patients developing dementia, and that need for partnership as well with other groups. But this reminder that it looks attaining or maintaining your brain health looks different at every stage of life. And so, you want to pick up on any elements of that and how we can better engage partners at that life stage?
Dr. Joel Salinas:
Yeah, you brought up a really important point about the role of psychiatric care within that patient and how it influenced their neurologic care. And it really speaks to what I would envision to be part of the future of brain health is where we have a lot more alliances across the different specialties and disciplines. Mental health is brain health, right? We're all trying to help to support the same organ system here.
And if we, as a neurologist, could come into the picture and say, "That's depression, that's not my camp." Right? If we had missed that, helping to improve that person's mood is actually going to help to improve their cognitive functioning and their independence, then we're not actually doing our role as a neurologist.
Dr. Lazar:
I also want to mention that atypical dementia and Alzheimer can present as agitation or anxiety, and they're just like atypical Alzheimer's. So it's very important to have a good assessment from a psychiatrist that we do know is dementia, not something else.
Dr. Gregg Day:
Agreed.
Dr. Joel Salinas:
Agreed.
Dr. Gregg Day:
Anyone else interested in catching? Evelyn, how's your arm? You want to throw all the way. This is brain health, laughter, exercise. We're getting it all. That's great.
Vineeta Singh:
Can you all hear me?
Dr. Gregg Day:
Yeah.
Vineeta Singh:
Great.
Dr. Gregg Day:
Please, go Ahead. Thank you.
Vineeta Singh:
This is Vineeta Singh. I am at University of California, San Francisco. I'm a critical care neurologist. And I love the idea of expanding on social determinants of brain health. It's not one monolith. It can be so vast. I work at the county hospital, and I'm in a trauma critical care unit.
What I have recently started doing with my medical students, because as you all know, you're also an educator, and very limited amount of time with your ICU patient, the student almost never gets to connect with the patient. I have started asking them to write up a note, social determinants of health for the patient that they're following, because their notes don't count toward my billing, but it does highlight so many other issues.
As you can imagine, trauma settings, it's like you have mental health disorder, substance use, trauma that you can make all kinds of Venn Diagram, and there's so much overlap. And this is just last three months, and I have uncovered so many things on my patients that I would not have known that we have been able to connect them to the proper services, whether it was for addiction, whether it was just the fear with all that's going on in our country.
Family members not being able to come visit their loved ones, and we didn't even know. We though this person was unidentified. No, they had a whole family. They just could not come. Just wanted to bring another angle to it. When you have limited amount of time, critical care, education, you can still do advocacy.
Dr. Gregg Day:
Well, let me thank you on behalf of the panel because that is such a phenomenal example of both education. You're educating and bringing new people into the brain health discussion through the medical students. It's an effective use of time. They're contributing valuable information, but it also shows what happens when we actually ask these questions to patients.
If it's in your mind and thinking, "Oh, this could be a very awkward conversation," our patients are open to these lines of discussion if we're leading them. And we learn things that, in the ICU, improves the health of the patient in front of you, but also all of those connected to the patient in that whole unit. And a wonderful example of a very pragmatic way to roll out brain health in an ICU practice that involves other generations of medical trainees and hopefully future neurologists.
Dr. Joel Salinas:
I would also just add, we often hear that there's not enough time to cover everything in day-to-day. How do we expect to train the future of neurology that really cares about all elements of a patient if they haven't been taught to value all these elements? So I really love that suggestion to have the residents actually have a section in the note about social determinants.
So even throughout your care, you can do a lot of modeling by actually asking questions that relate to these factors or bring it up as they're presenting if they asked about it, because then that kind of communicates that this is important. And so as a field, as a clinician, you need to be thinking about these things.
Dr. Gregg Day:
Other comment, question here?
Hannah Noah:
Yeah. I'm Hannah Noah, Behavioral Neurology at UNC. So I'm blessed with hour-long appointment slots. And even then, it's a lot to get through. You have to tell this person they have Alzheimer's and to talk about that, the potential emotional fallout, and then you have to get through. But usually, my approach for talking about what we do about it is, let's talk about brain health, then let's talk about cholinesterase inhibitors, let's talk about infusions if those are applicable.
So even with my nice long appointment slots, it's still five, 10 minutes absolute maximum to go through all of brain health. And to get around this, I'm interested in actually starting a program, types of visits that are just solely dedicated to brain health and preventative neurology, not so much just the diagnostic, the medical treatment, just solely on that preventative space. So I've gotten to know a couple of people who have done this.
It seems like the group visit model is something that's worked well for some people. I'm trying to get to know a couple of people who are certified in lifestyle medicine who are doing similar things. So my question for you guys is, do you know anybody who has successfully done a brain health?
Dr. Joel Salinas:
Two points to what you said. I think the point that you made about not having enough time even though you have an hour. And actually, I recently heard about somebody that does behavioral neurology, and they get 90-minute slots, and I was like-
Dr. Gregg Day:
There's 90-minute slots out there.
Dr. Joel Salinas:
Yeah, that's wild. But yeah, some places do that. What a luxury. But one thing I learned from, this came from Allan Roper, was just don't try to boil the ocean in a single visit. And for those of you who worry about having enough time, what I will do in my note, the things that I couldn't get to, I put it as a part of my assessment and plan and say, "In follow-up, we'll address the following." That way when I do the follow-up, I can make sure, oh, yeah, this is my missing agenda that I can bring back into this visit.
But for doing these kind of brain health type of visits, so there's really great models in this within lifestyle medicine. And shared medical appointments, these kind of group appointments, there's been a lot of research around group level interventions. And the socialization aspect of it really helps with kind of group norms and with education, and people get to participate more and hear questions that others didn't ask. I would say that the coverage of it is actually probably better than you anticipate.
So you have to just really think through within your own clinical practice, what is the ideal system that you can put around it? It may take a little bit of training around staff to make sure that the workflow makes sense because you want it to be really smooth. We do it all via virtual visit because we're fully telehealth, and we found it helpful to set it up within a structured kind of modular program. And that's another lesson from U.S. POINTER, which is structured programs tend to do better.
Dr. Gregg Day:
Something else we need to remember, that 60-minute visit, I won't say that's a luxury. As you described, all the things we try to accomplish. How much does the patient really hear after we say the words Alzheimer Disease, or stroke, or multiple sclerosis or put your disease in there? For many patients, it becomes white noise after. It's overwhelming. And so, setting up and planning for this dedicated visit is really what we want to see for our patients, and there's many ways to do this.
This is a phenomenal way that you're doing it. Leveraging those virtual resources, that means other people can be involved in the discussion. They don't even have to be in the same location. They can come in from across the country, creates that time and that space. In our clinic, we do a brain health visit. It's funded through state level funding to advance brain health, which is unique. And we're really privileged to have that.
And it's run by a research educator who we've trained and worked through some of these goals as well. And so, there are many novel ways to do this. We want to see this moving forward. Well, we've got one more from Dr. Kingston. We're going to make sure he gets it in. And then, we're going to go back to our panel here. From the University of Toronto.
Dr. Kingston:
Yeah, so my lens is obviously a bit different because I see younger patients who have a lot of subjective complaints. And I'm also spoiled listening to this because we have 90-minute appointments for new patients that are paid for by the government, so it's actually very nice for us. But what I'll do is, a lot of migraine patients have heard it all. It's not the water you drank, it's not the sleep you got that's causing your migraine.
So it's a good opportunity to tell people with migraine that poor self-care is not causing your migraine, but how can we reframe this and use this as a good opportunity to maximize your general health? Because we know when your general health is better, so is migraine. And that can be a good way to get people involved in brain health when they're younger.
Dr. Gregg Day:
An amazing transition point. You're effectively preventing strokes and maybe preventing dementia and other visits down the road. I'm glad I haven't heard anyone express concern that if we do such a great job with this, we're all going to be out of a job. We appreciate that there's plenty of patients that need to see us, and it's a privilege to be able to engage in something that's going to advance their health and the health of their family.
Talking about success though, what would success look like? And the question that I wanted to end on, and I want to hear from both of you here, if we look 10 years ahead and we assume that this AAN Brain Health Initiative is wildly successful, what would be one visible way that the daily practice of neurology is going to look fundamentally different from today? And Sarah, I'll let you lead with that.
Dr. Sarah Song:
It would be great if we were able to actually track sort of a longitudinal path for each patient and say, "You know what? You were here. Last time I saw you six months ago, but now you're here for these reasons." Right? And that wouldn't be a weird thing for them to hear about how their brain health is doing or how their brain health has been improving because of different things that they have been doing. And that brain health would really just be part of the vernacular of just a normal visit. It's not stroke visit plus brain health check. It's just stroke and brain health, right? So it's all in one. That would be amazing.
Dr. Joel Salinas:
I would envision within 10 years, one really powerful way to see how brain health has impacted care is that we're not just thinking about what can I do today, but what have we helped to prevent in the future and having a way to really quantify that, just understanding the risk reduction. Or having maybe through the use of potentially being able to show kind of what the counterfactual would've looked like if we hadn't implemented these things, how much have we now benefited you or saved you from? I do think that there's a lot of hope for brain health.
But I do think that there's a lot of very real barriers that we still need to tackle for that to be successful. The pillars of brain health really speak to that. We do need better research really focused around that. We need to have better health systems that anchor around, a focus around health. We need payment models and payers to really see this as something really valuable, so that way, we can actually be compensated for that. To some degree, education and the culture of how we practice needs to change.
Dr. Gregg Day:
Just going to put a word to that. We want brain health to be top of mind for everyone at this meeting. It shouldn't be a new concept or a new vision. And the priorities that you've set are absolutely in line with what we're trying to achieve through the brain health committee and through the other AAN leaderships, and ultimately through our members.
As we wrap the panel discussion, I just want to conclude really remembering this central theme that we've been talking about today. Brain health is not that additional task. It's a framework that we can use to reorganize our visit, reorganize our approach, and ultimately continue to do what we're already committed to do across the lifespan.
What we've heard from our panelists, and thank you to many in the audience who have contributed to that as well, this clearly reflects the AAN's vision for brain health. Integrating brain health doesn't require us to do everything. That's not what we want you to leave with.
But I do want you to leave recognizing that you're a leader in this space, and that we are the best ones to lead, to help our patients prioritize what they can do next, and to walk with them along the treatment of disease, but also heading towards the prevention of neurologic disease and maintenance and attaining of their goals through the lifespan as we work on the system challenges, the environment, and education.
I do hope that today's discussion leaves each of you with maybe one practical thing that you can take home to expand the discussion with other people in your practice, maybe to make a difference, even if it's not a 90-minute visit. We've only got a few of those in the crowd here, but great space to continue to advocate and advance.
And on behalf of the American Academy of Neurology and certainly on behalf of the Brain Health Committee, I really want to thank each of our panelists, of course. I love the discussion with you guys. It's always a pleasure to talk about things that we're passionate about. Thanks.
Dr. Stacey Clardy:
This is Stacey Clardy, your Podcast Editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword in your podcast app for any neurology specific topics you want to learn about.